DESCRIPTION: The vascular complications of diabetes are the most serious manifestations of the disease and account for most of its morbidity and mortality. Major obstacles to developing therapeutic approaches are the lack of biomarkers for tracking the onset, progression, and extent of tissue damage, and insufficient knowledge of the effect of treatments on a cellular or molecular level in vivo. Our approach to advancing the early diagnosis and treatment of diabetes vascular complications is through visualizing and targeting vascular molecular pathology before structural damages occurs. We established the first and currently only existing in vivo technology for the detection of specific molecules on the vascular endothelium, and used it to identify novel early vascular disease biomarkers. Using our technology, we established vascular endothelial growth factor receptor 2 (VEGFR-2) as a novel biomarker for early diagnosis of diabetic retinopathy. Understanding the early processes in diabetic retinopathy may be a window to subclinical diagnosis of systemic complications of diabetes. Our preliminary data show novel expression of Kidney Injury Molecule-1 (KIM-1) in the vascular endothelium in the retina, brain, liver, kidney, lung and aorta of diabetic animals, but not in normal control. Molecular imaging of KIM-1 in retinal vessels could become a powerful target in evaluating early stages of diabetes complications. Our ultimate goal is to non-invasively detect and target signs of diabetes vascular complications at the earliest possible stage in human patients. The aims of the proposed research are: 1) establish an association between retinal markers and other organs, 2) optimize our molecular imaging and nano-probe technology for detection of retinal endothelial markers in humans, and 3) directly image nano-probe accumulation in various organs of diabetic animals, using multi-modality molecular imaging. The completion of the research will facilitate 1) subclinical diagnosis of diabetes vascular complications before irreversible structural damages occur, 2) the tracking of progression, and extent of organ manifestations in diabetic individuals, and 3) the development of novel therapeutic approaches.